Hair Follicle Stem Cell-Specific PPARγ Deletion Causes Scarring Alopecia
Open accessAbstract
Primary cicatricial or scarring alopecias (CA) are a group of inflammatory hair disorders of unknown pathogenesis characterized by the permanent destruction of the hair follicle. The current treatment options are ineffective in controlling disease progression largely because the molecular basis for CA is not understood. Microarray analysis of the lymphocytic CA, Lichen planopilaris (LPP), compared to normal scalp biopsies identified decreased expression of genes required for lipid metabolism and peroxisome biogenesis. Immunohistochemical analysis showed progressive loss of peroxisomes, proinflammatory lipid accumulation, and infiltration of inflammatory cells followed by destruction of the pilosebaceous unit. The expression of peroxisome proliferator-activated receptor (PPAR) gamma, a transcription factor that regulates these processes, is significantly decreased in LPP. Specific agonists of PPARgamma are effective in inducing peroxisomal and lipid metabolic gene expression in human keratinocytes. Finally, targeted deletion of PPARgamma in follicular stem cells in mice causes a skin and hair phenotype that emulates scarring alopecia. These studies suggest that PPARgamma is crucial for healthy pilosebaceous units and it is the loss of this function that triggers the pathogenesis of LPP. We propose that PPARgamma-targeted therapy may represent a new strategy in the treatment of these disorders.
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PGC1α interacts with PPARγ, and PPARγ dysregulation in hair follicle stem cells produces results similar to scarring alopecia.
“PGC1α also interacts with PPARγ, and dysregulation of PPARγ has been shown in hair follicle stem cells (HFSCs) to produce similar results to scarring alopecia (i.e., hair loss disorder) (Karnik et al., 2009).”
From Comprehensive Multi-omics Analysis Reveals Mitochondrial Stress as a Central Biological Hub for Spaceflight Impact (2020) · cites this paper as Karnik et al., 2009
The Introduction and Discussion (page numbers unavailable) report that deleting PPARγ in mouse hair follicle stem cells causes scarring alopecia resembling human disease. The cited paper’s passages do not establish the separate claim that PGC1α interacts with PPARγ. (LLM, conf=0.88)
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“PGC1α also interacts with PPARγ, and dysregulation of PPARγ has been shown in hair follicle stem cells (HFSCs) to produce similar results to scarring alopecia (i.e., hair loss disorder) (Karnik et al., 2009).”
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- Authors
- Karnik, P., Tekeste, Z., McCormick, T. S., Gilliam, A. C., Price, V. H., Cooper, K. D., & Mirmirani, P.
- Affiliations
- University Hospitals Cleveland Medical Center (US)
- University of California, San Francisco (US)
- Corresponding author
- Karnik, Pratima
- Venue
- Journal of Investigative Dermatology
- Publisher
- Elsevier BV
- Published
- 2009-05
- Volume
- 129
- Issue
- 5
- Pages
- 1243-1257
- ISSN
- 0022-202X (ISSN-L)
- PMC
- PMC3130601
- OpenAlex
- W2080345081
- Cited by
- 321
- References
- 43
- Citations by year
- 2026: 14 · 2025: 16 · 2024: 26 · 2023: 17 · 2022: 41 · 2021: 18 · 2020: 14 · 2019: 22 · 2018: 20 · 2017: 17 · 2016: 14 · 2015: 14 · 2014: 13 · 2013: 21 · 2012: 16
- FWCI
- 15.28
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Investigative Dermatology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- American Skin Association
- Vanderbilt University
- Case Western Reserve University (P30 CA43703)
- National Institutes of Health (AR39750, CA43703)
- School of Medicine, Vanderbilt University
- National Cancer Institute (P-30 CA43703, P30CA043703)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (P30AR039750, P30 AR39750, R01AR056245)
- Topics
- Health Sciences › Medicine › Urology › Hair Growth and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › melanin and skin pigmentation
- Keywords
- scarring alopecia, lichen planopilaris, PPARγ, hair follicle stem cells, peroxisome biogenesis, lipid metabolism, pilosebaceous unit, PPARγ agonists, keratinocytes, targeted therapy
- MeSH terms
- Alopecia, Animals, Cicatrix, Disease Models, Animal, Humans, Lichen Planus, Stem Cells, Case-Control Studies, Gene Deletion, Mice, Knockout, Hair Follicle, Peroxisomes, Microarray Analysis, PPAR gamma, Lipid Metabolism, Mice
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